AB1464 THE ROLE OF EPSTEIN-BARR VIRUS ACTIVITY IN RHEUMATOID ARTHRITIS AND OSTEOARTHRITIS PATIENTS
Authors: A. Banko, D. Miljanovic, I. Jeremic, M. Basarić, M. Grk, I. Lazarevic, R. Miskovic, A. Cirkovic
Journal: Annals of the Rheumatic Diseases (2022)

Background Rheumatoid arthritis (RA) is one of the most common autoimmune diseases with a 1% worldwide prevalence (1) and still elusive etiology (2). Epstein-Barr virus (EBV) evidently plays an important role in the pathogenesis of autoimmune diseases by molecular mimicry, bystander activation effect or epitope-spreading (3). However, cause/effect relationship between EBV and RA is still missing. Objectives The aims of this study were to explore the association between EBV infection activity, findings of autoantibodies and markers of acute inflammation in patients with two most prevalent diseases of joints, autoimmune RA and degenerative osteoarthritis (OA). Methods A blood samples of 89 seropositive RA patients, 64 newly diagnosed (RAa) and 25 with poorly controlled disease (RAb) (unsuccessfully methotrexate treatment ≥ 6 months), and 50 OA were enrolled. The complete anti-EBV serological panel was detected by commercial ELISA kits. Nested-PCR was used for detection of EBV DNA. Clinical data, biochemical and immunological parameters were obtained from electronic medical records. Complete statistical analysis was performed in IBM SPSS ver. 21. Results The average age of all patients was 61.54±11.77 years (p=0.007) with predominant female gender in all groups, 81.3% (p=0.139). Anti-EBNA1 IgG antibodies were present in 95%, 92%, and 98% (p=0.474), anti-EBV-CA IgG antibodies in 98%, 60%, and 100% (p&lt;0.001), anti-EBV-CA IgM antibodies in 25%, 40%, and 4% (p=0.008), anti-EBV-EA IgG antibodies in 14.1%, 20%, and 4% (p=0.084), and anti-EBV-EA IgM antibodies in 20%, 16%, and 6% (p=0.094) in RAa, RAb, and OA, respectively. There was statistically significant difference in the titer of anti-EBV-CA IgG and IgM antibodies between all three groups (p=0.001 and p=0.007, respectively). According to serology findings active EBV infection was present in 47.5%, 40%, and 12% in RAa, RAb, and OA, respectively (p&lt;0.001). On the other hand, corresponding to PCR results only, active EBV infection was detected in 6.3%, 0%, and 20% in RAa, RAb, and OA, respectively (p=0.010). There was statistically significant difference in way of detecting active EBV infection based on serology or PCR only (p&lt;0.001). Further analysis showed that over 80% of all RA patients (81% in RAa and 96% in RAb), whilst 48% of OA had elevated values of sedimentation (SE) (p&lt;0.001). C-reactive protein (CRP) was raised in 83% RA (79% in RAa and 100% in RAb) and in 26.5% of OA patients (p&lt;0.001). The majority of all RA patients had elevated rheumatoid factor (RF) and ACPA (84% and 92%) with no difference between RAa and RAb patients (p=0.361 and p=0.203, respectively). Among patients with active EBV infection (based on both serology and PCR results), there was a significantly higher level of anticardiolipin IgG (p=0.012) and anticardiolipin IgM (p=0.009) autoantibodies in RAa patients, while the level of SSA autoantibodies (p=0.024) was higher in RAb patients. On the other side, there was no significant difference in the level of any autoantibody or factors of acute inflammation (SE and CRP) in patients with past EBV infection. Conclusion This study demonstrated linkage between an active EBV infection and elevation of some autoantibodies in RA pathogenesis. As EBV DNA was not found only in a group of RA patients under immunosuppressive therapy, it’s suggested that EBV clearing from blood could be direct consequence of methotrexate use. Collectively, these findings indicate that determining of EBV activity must be based on both serology and molecular methods in order not to oversee EBV reactivation during follow-up of these patients. References [1]Balandraud N, Roudier J. Epstein-Barr virus and rheumatoid arthritis. Joint Bone Spine. 2018;85:165-170. [2]Ball RJ, Avenell A, Aucott L, Hanlon P, Vickers MA. Systematic review and meta-analysis of the sero-epidemiological association between Epstein-Barr virus and rheumatoid arthritis. Arthritis Res Ther. 2015;29:274. [3]Houen G, Trier NH. Epstein-Barr Virus and Systemic Autoimmune Diseases. Front Immunol. 2021;7:587380. Acknowledgements This research was supported by the Science Fund of the Republic of Serbia, PROMIS, No 6060866, ROLERS. Disclosure of Interests None declared